tbuckley/cabot-search huggingface dataset:
HILPDA promotes NASH-driven HCC development by restraining intracellular fatty acid flux in hypoxia
Authors: Davide Povero, Yongbin Chen, Scott M. Johnson, Cailin E. McMahon, Meixia Pan, Hanmei Bao, Xuan-Mai T. Petterson, Emily Blake, Kimberly P. Lauer, Daniel R. O’Brien, Yue Yu, Rondell P. Graham, Timucin Taner, Xianlin Han, Gina L. Razidlo, Jun Liu
Journal: Journal of Hepatology (2023)
Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies
Authors: S. Hobson, S. Arefin, A. Witasp, L. Hernandez, K. Kublickiene, P.G. Shiels, P. Stenvinkel
Journal: Circulation Research (2023)

The pathophysiology of vascular disease is linked to accelerated biological aging and a combination of genetic, lifestyle, biological, and environmental risk factors. Within the scenario of uncontrolled artery wall aging processes, CKD (chronic kidney disease) stands out as a valid model for detailed structural, functional, and molecular studies of this process. The cardiorenal syndrome relates to the detrimental bidirectional interplay between the kidney and the cardiovascular system. In addition to established risk factors, this group of patients is subjected to a plethora of other emerging vascular risk factors, such as inflammation, oxidative stress, mitochondrial dysfunction, vitamin K deficiency, cellular senescence, somatic mutations, epigenetic modifications, and increased apoptosis. A better understanding of the molecular mechanisms through which the uremic milieu triggers and maintains early vascular aging processes, has provided important new clues on inflammatory pathways and emerging risk factors alike, and to the altered behavior of cells in the arterial wall. Advances in the understanding of the biology of uremic early vascular aging opens avenues to novel pharmacological and nutritional therapeutic interventions. Such strategies hold promise to improve future prevention and treatment of early vascular aging not only in CKD but also in the elderly general population.
The epidemiology of Shiga toxin-producing Escherichia coli O26:H11 (clonal complex 29) in England, 2014–2021
Authors: Ella V Rodwell, Alex Simpson, Yung-Wai Chan, Gauri Godbole, Noel D McCarthy, Claire Jenkins
Journal: Journal of Infection (2023)

We aimed to describe the genomic epidemiology of the foodborne gastrointestinal pathogen, Shiga toxin-producing Escherichia coli (STEC) serotype O26:H11 belonging to clonal complex 29 (CC29) in England.Between 01 January 2014 and 31 December 2021, 834 human isolates belonging to CC29 were sequenced at the UK Health Security Agency, and the genomic data was integrated with epidemiological data.Diagnoses of STEC O26:H11 in England have increased each year from 19 in 2014 to 144 in 2021. Most isolates had the Shiga toxin subtype profiles stx1a (47%), stx1a,stx2a (n = 24%) or stx2a (n = 28%). Most cases were female (57%), and the highest proportion of cases belonged to the 0-5 age group (38%). Clinical symptoms included diarrhoea (93%), blood-stained stool (48%), and abdominal pain (74%). Haemolytic Uraemic Syndrome (HUS) was diagnosed in 40/459 (9%) cases and three children died. All isolates causing STEC-HUS had stx2a either alone (n = 33) or in combination with stx1a (n = 7).STEC O26:H11 are a clinically significant, emerging threat to public health in England. Determining the true incidence and prevalence is challenging due to inconsistent national surveillance strategies. Improved diagnostics and surveillance algorithms are required to monitor the true burden, detect outbreaks and to implement effective interventions.
SARS-CoV-2 variant-dependent inflammasome activation
Authors: Elisa Teyssou, Stéphane Marot, Adélie Gothland, Isabelle Malet, Karen Zafilaza, Valentin Leducq, Théophile Cocherie, Eve Todesco, Cathia Soulié, Anne-Geneviève Marcelin, Vincent Calvez
Journal: Journal of Infection (2023)
CX3CR1<sup>+</sup>Alveolar Macrophages: A New Player in Lung Eosinophil Homeostasis
Authors: Bouchaib Lamkioued, Abdelilah S. Gounni
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"CX3CR1+ Alveolar Macrophages: A New Player in Lung Eosinophil Homeostasis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Single-nucleus RNA sequencing of pre-malignant liver reveals disease-associated hepatocyte state with HCC prognostic potential
Authors: Rodrigo Carlessi, Elena Denisenko, Ebru Boslem, Julia Köhn-Gaone, Nathan Main, N. Dianah B. Abu Bakar, Gayatri D. Shirolkar, Matthew Jones, Aaron B. Beasley, Daniel Poppe, Benjamin J. Dwyer, Connie Jackaman, M. Christian Tjiam, Ryan Lister, Michael Karin, Jonathan A. Fallowfield, Timothy J. Kendall, Stuart J. Forbes, Elin S. Gray, John K. Olynyk, George Yeoh, Alistair R.R. Forrest, Grant A. Ramm, Mark A. Febbraio, Janina E.E. Tirnitz-Parker
Journal: Cell Genomics (2023)
A commentary on ‘Indications, trends, and perioperative outcomes of minimally invasive liver surgery in non-obese and obese patients: an international multicenter propensity score-matched retrospective cohort study of 9963 patients’
Authors: Xingru Wang
Journal: International Journal of Surgery (2023)

Department of Hepatobiliary Surgery, Qujing Second People's Hospital of Yunnan Province, Qujing, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Hepatobiliary Surgery, Qujing Second People's Hospital of Yunnan Province, Qujing, China, Tel: +8615887473369. E-mail address: [email protected] (X. Wang). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Neural circuit changes in neurological disorders: Evidence from in vivo two-photon imaging
Authors: Huan Xiong, Fei Tang, Yujie Guo, Ruxiang Xu, Peng Lei
Journal: Ageing Research Reviews (2023)

Neural circuits, such as synaptic plasticity and neural activity, are critical components of healthy brain function. The consequent dynamic remodeling of neural circuits is an ongoing procedure affecting neuronal activities. Disruption of this essential process results in diseases. Advanced microscopic applications such as two-photon laser scanning microscopy have recently been applied to understand neural circuit changes during disease since it can visualize fine structural and functional cellular activation in living animals. In this review, we have summarized the latest work assessing the dynamic rewiring of postsynaptic dendritic spines and modulation of calcium transients in neurons of the intact living brain, focusing on their potential roles in neurological disorders (e.g. Alzheimer's disease, stroke, and epilepsy). Understanding the fine changes that occurred in the brain during disease is crucial for future clinical intervention developments.
The role of the gut microbiome in the development of hepatobiliary cancers
Authors: Neil Daniel, Flavia Genua, Mazda Jenab, Ana-Lucia Mayén, Anastasia Chrysovalantou Chatziioannou, Pekka Keski-Rahkonen, David J. Hughes
Journal: Hepatology (2023)

Hepatobiliary cancers, including hepatocellular carcinoma and cancers of the biliary tract, share high mortality and rising incidence rates. They may also share several risk factors related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and rates of obesity. Recent data also suggest a role for the gut microbiome in the development of hepatobiliary cancer and other liver pathologies. The gut microbiome and the liver interact bidirectionally through the "gut-liver axis," which describes the interactive relationship between the gut, its microbiota, and the liver. Here, we review the gut-liver interactions within the context of hepatobiliary carcinogenesis by outlining the experimental and observational evidence for the roles of gut microbiome dysbiosis, reduced gut barrier function, and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to hepatobiliary cancer development. We also outline the latest findings regarding the impact of dietary and lifestyle factors on liver pathologies as mediated by the gut microbiome. Finally, we highlight some emerging gut microbiome editing techniques currently being investigated in the context of hepatobiliary diseases. Although much work remains to be done in determining the relationships between the gut microbiome and hepatobiliary cancers, emerging mechanistic insights are informing treatments, such as potential microbiota manipulation strategies and guiding public health advice on dietary/lifestyle patterns for the prevention of these lethal tumors.
60 years of healthy aging: On definitions, biomarkers, scores and challenges
Authors: Luise Charlotte Behr, Andreas Simm, Alexander Kluttig, Anne Grosskopf Großkopf
Journal: Ageing Research Reviews (2023)

As the proportion of aging people in our population increases steadily, global strategies accompanied by extensive research are necessary to tackle society and health service challenges. The World Health Organization recently published an action plan: "Decade of healthy aging 2020-2030", which calls for concerted collaboration to prevent poverty of older people to provide quality education, job opportunities, and an age-inclusive infrastructure. However, scientists worldwide still struggle to find definitions and appropriate measurements of aging per se and healthy aging in particular. This literature review aims to compile concepts of healthy aging and provide a condensed overview of the challenges in defining and measuring it, along with suggestions for further research.We conducted three independent systematic literature searches covering the main scopes addressed in this review: (1) concepts and definitions of healthy aging, (2) outcomes and measures in (healthy) aging studies and (3) scores and indices of healthy aging. For each scope, the retrieved literature body was screened and subsequently synthesized.We provide a historical overview of the concepts of healthy aging over the past 60 years. Furthermore, we identifiy current difficulties in identifying healthy agers, including dichotomous measurements, illness-centered views, study populations & designs. Secondly, markers and measures of healthy aging are discussed, including points to consider, like plausibility, consistency, and robustness. Finally, we present healthy aging scores as measurements, which combine multiple aspects to avoid a dichotomous categorization and display the bio-psycho-social concept of healthy aging.When deducting research, scientists need to consider the diverse challenges in defining and measuring healthy aging. Considering that, we recommend scores that combine multiple aspects of healthy aging, such as the Healthy Ageing Index or the ATHLOS score, among others. Further efforts are to be made on a harmonized definition of healthy aging and validated measuring instruments that are modular, easy to apply and provide comparable results in different studies and cohorts to enhance the generalization of results.
Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance
Authors: Tomer Milo, Yael Korem Kohanim, Yoel Toledano, Uri Alon
Journal: Trends in Immunology (2023)

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are common autoimmune diseases of the thyroid gland, causing hyperthyroidism and hypothyroidism, respectively. Despite their opposing clinical manifestation, they have several enigmatic links. Here, we propose that GD and HT have the same fundamental origin: both diseases are the cost of a beneficial physiological process called autoimmune surveillance of hypersecreting mutants. Autoreactive T cells selectively eliminate mutant cells that hypersecrete the hormones and threaten to become toxic nodules. These T cells can trigger a humoral response in susceptible individuals, leading to the production of antibodies against thyroid antigens. This shared origin can explain similarities in incidence and risk factors between HT and GD, despite their opposite clinical phenotypes.
Liver resection versus transarterial chemoembolisation for the treatment of intermediate hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Aleksandar Bogdanovic, Jelena Djokic Kovac, Predrag Zdujic, Uros Djindjic, Vladimir Dugalic
Journal: International Journal of Surgery (2023)

Background: Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. Methods: A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3 cm. The main outcome was OS, expressed as the hazard ratio. Results: Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39–0.69; I 2 =79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34–0.59; I 2 =55%). Conclusion: Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials.
Assessment of heterogeneity among participants in the Parkinson's Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study
Authors: Andrew Siderowf, Luis Concha-Marambio, David-Erick Lafontant, Carly M Farris, Yihua Ma, Paula A Urenia, Hieu Nguyen, Roy N Alcalay, Lana M Chahine, Tatiana Foroud, Douglas Galasko, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Kathleen L Poston, John Seibyl, Tanya Simuni, Caroline M Tanner, Daniel Weintraub, Aleksandar Videnovic, Seung Ho Choi, Ryan Kurth, Chelsea Caspell-Garcia, Christopher S Coffey, Mark Frasier, Luis M A Oliveira, Samantha J Hutten, Todd Sherer, Kenneth Marek, Claudio Soto
Journal: The Lancet Neurology (2023)
Reply to Kari Hemminki, Jianguang Ji, and Jan Sundquist’s Letter to the Editor re: Mark N. Brook, Holly Ní Raghallaigh, Koveela Govindasami, et al. Family History of Prostate Cancer and Survival Outcomes in the UK Genetic Prostate Cancer Study. Eur Urol 2023;83:257–66
Authors: Mark N. Brook, Holly Ní Raghallaigh, Zsofia Kote-Jarai, Rosalind A. Eeles
Journal: European Urology (2023)
Quantization of extraoral free flap monitoring for venous congestion with deep learning integrated iOS applications on smartphones: a diagnostic study
Authors: Shao-Yun Hsu, Li-Wei Chen, Ren-Wen Huang, Tzong Yueh Tsai, Shao-Yu Hung, David Chon-Fok Cheong, Johnny Chuieng-Yi Lu, Tommy Nai-Jen Chang, Jung-Ju Huang, Chung-Kan Tsao, Chih-Hung Lin, David Chwei-Chin Chuang, Fu-Chan Wei, Huang-Kai Kao
Journal: International Journal of Surgery (2023)

Free flap monitoring is essential for postmicrosurgical management and outcomes but traditionally relies on human observers; the process is subjective and qualitative and imposes a heavy burden on staffing. To scientifically monitor and quantify the condition of free flaps in a clinical scenario, we developed and validated a successful clinical transitional deep learning (DL) model integrated application.
NETs-Induced Thrombosis Impacts on Cardiovascular and Chronic Kidney Disease
Authors: Manovriti Thakur, Carolina Victoria Cruz Junho, Sarah Maike Bernhard, Marc Schindewolf, Heidi Noels, Yvonne Döring
Journal: Circulation Research (2023)

Arterial and venous thrombosis constitute a major source of morbidity and mortality worldwide. Association between thrombotic complications and cardiovascular and other chronic inflammatory diseases are well described. Inflammation and subsequent initiation of thrombotic events, termed immunothrombosis, also receive growing attention but are still incompletely understood. Nevertheless, the clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is evident by an increased risk of thrombosis and cardiovascular events in patients with inflammatory or infectious diseases. Proinflammatory mediators released from platelets, complement activation, and the formation of NETs (neutrophil extracellular traps) initiate and foster immunothrombosis. In this review, we highlight and discuss prominent and emerging interrelationships and functions between NETs and other mediators in immunothrombosis in cardiovascular disease. Also, with patients with chronic kidney disease suffering from increased cardiovascular and thrombotic risk, we summarize current knowledge on neutrophil phenotype, function, and NET formation in chronic kidney disease. In addition, we elaborate on therapeutic targeting of NETs-induced immunothrombosis. A better understanding of the functional relevance of antithrombotic mediators which do not increase bleeding risk may provide opportunities for successful therapeutic interventions to reduce thrombotic risk beyond current treatment options.
Bone-derived MSCs encapsulated in alginate hydrogel prevent collagen-induced arthritis in mice through the activation of adenosine A2A/2B receptors in tolerogenic dendritic cells
Authors: Gaona Shi, Yu Zhou, Wenshuai Liu, Chengjuan Chen, Yazi Wei, Xinlong Yan, Lei Wu, Weiwei Wang, Lan Sun, Tiantai Zhang
Journal: Acta Pharmaceutica Sinica B (2023)

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39+CD73+ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.
Management of Rheumatoid Arthritis With a Digital Health Application
Authors: Chun Li, Jianlin Huang, Huaxiang Wu, Fen Li, Yi Zhao, Zhenchun Zhang, Shengguang Li, Hua Wei, Miaojia Zhang, Hongsheng Sun, Jing Yang, Qin Li, Xiaomei Li, Wufang Qi, Wei Wei, Yasong Li, Zhenbin Li, Yongfu Wang, Fengxiao Zhang, Henglian Wu, Zongwen Shuai, Zhenbiao Wu, Yi Li, Shengsong Jia, Yuhua Jia, Fei Xiao, Rong Mu, Zhanguo Li
Journal: JAMA Network Open (2023)

IMPORTANCE Digital health applications have been shown to be effective in the management of chronic diseases with simple treatment targets. The potential clinical value of digital health applications in rheumatoid arthritis (RA) has not been well studied. OBJECTIVE To investigate whether assessing patient-reported outcomes using digital health applications could result in disease control for patients with RA. DESIGN, SETTING, AND PARTICIPANTS This is a multicenter, open-label randomized clinical trial in 22 tertiary hospitals across China. Eligible participants were adult patients with RA. Participants were enrolled from November 1, 2018, to May 28, 2019, with a 12-month follow-up. The statisticians and rheumatologists who assessed disease activity were blinded. Investigators and participants were not blind to group assignment. Analysis was conducted from October 2020 to May 2022. INTERVENTIONS Participants were randomly assigned at a 1:1 ratio (block size of 4) to a smart system of disease management group (SSDM) or a conventional care control group. Upon the completion of the 6-month parallel comparison, patients in the conventional care control group were instructed to use the SSDM application for an extension of 6 months. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of patients with disease activity score in 28 joints using the C-reactive protein (DAS28-CRP) of 3.2 or less at month 6. RESULTS Of 3374 participants screened, 2204 were randomized, and 2197 patients with RA (mean [SD] age, 50.5 [12.4] years; 1812 [82.5%] female) were enrolled. The study included 1099 participants in the SSDM group and 1098 participants in the control group. At month 6, the rate of patients with DAS28-CRP of 3.2 or less was 71.0% (780 of 1099 patients) in the SSDM group vs 64.5% (708 of 1098 patients) in the control group (difference between groups, 6.6%; 95% CI, 2.7% to 10.4%; P = .001). At month 12, the rate of patients with DAS28-CRP of 3.2 or less in the control group increased to a level (77.7%) that was comparable with that (78,2%) in the SSDM group (difference between groups, −0.2%; 95% CI, −3.9% to 3.4%; P = .90). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of RA, the use of a digital health application with patient-reported outcomes was associated with an increase in disease control rate. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03715595
Risk of Type 1 Diabetes in Children Is Not Increased After SARS-CoV-2 Infection: A Nationwide Prospective Study in Denmark
Authors: Rohina Noorzae, Thor Grønborg Junker, Anders Peter Hviid, Jan Wohlfahrt, Sjurdur Frodi Olsen
Journal: Diabetes Care (2023)

It has been hypothesized that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children can increase risk of developing type 1 diabetes.We undertook a prospective, register-based analysis of children in Denmark by investigating the association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes. During the pandemic, Denmark had one of the highest test rates per capita in the world, and 90% of all Danish children were tested.Compared with children with a history of only negative SARS-CoV-2 tests, we did not observe a higher risk of first-time diagnosis of type 1 diabetes in children 30 days or more after a positive SARS-CoV-2 test (hazard ratio 0.85; 95% CI 0.70-1.04).Our data do not support that SARS-CoV-2 infection is associated with type 1 diabetes or that type 1 diabetes should be a special focus after a SARS-CoV-2 infection in children.